Tubal factor infertility is a common gynecological problem, responsible for 15-30 percent of all infertility. Most cases of tubal factor infertility are caused by Chlamydia trachomatis. Chlamydia is the most common sexually transmitted disease in the United States. Upper genital tract infections with Chlamydia are often asymptomatic or subclinical but can result in fallopian tube damage. These obligate intracellular microorganisms elude host defenses causing a persistent indolent infection. While multiple epidemiological studies have shown a link between Chlamydia and infertility, the underlying immunology and pathogenesis is poorly understood. Recent research has shown that an antibody response to the chlamydial 60-kilodalton heat shock protein (hsp 60) is associated with tubal factor infertility. Another 10-kilodalton heat shock protein (hsp 10) has been recently described. Our initial studies would indicate that infertile women also have antibodies to this chlamydial antigen. The central hypothesis of this research plan is that an altered immune response to chlamydial heat shock proteins is responsible for tubal factor infertility. The specific aims for this project are 1) to determine lymphocyte responses to hsp 10 and hsp 60 in women with tubal factor infertility and 2) to study expression of hsp 10 and hsp 60 in an in vitro model of fallopian tube infection. This research plan is part of a NICHD Mentored Clinical Scientist Development Award. The candidate for this award, Dr. Kevin Ault, is a clinically trained gynecologist. His interest in infectious diseases is the result of caring for women with tubal factor infertility. Other common gynecological diseases, such as ectopic pregnancy and pelvic inflammatory disease, have also been linked to infection with Chlamydia. By training gynecologists to apply fundamental techniques in immunology and microbiology to the problem of Chlamydia and infertility, we can have a better understanding of this common problem in women's health.